The overall objectives of this research are to develop a unified theory of genetic control that incorporates both nuclear and cytoplasmic genetic systems. For this purpose, we are using primarily the unicellular eukaryotic microorganism Chlamydomonas as a model system; some studies are also being carried out with mammalian cells in culture. One specific aim is to establish the molecular basis of maternal inheritance of organelle DNAs by looking for modification and restriction enzyme activities in zygotes of Chlamydomonas. We have already progressed in this direction. A site-specific restriction endonuclease and a site-specific methyl transferase have been isolated from Chlamydomonas. Studies of their modes of action are in progress, using both synthetic and naturally occurring polynucleotides, nuclear and organelle DNAs as substrates. A second aim is to compare the role of organelle proteins of Chlamydomonas and of mammalian cells in regulating the synthesis of nuclear DNA and thereby the cell cycle. A third aim is to examine the cytoplasmic tranmission in a mammalian cell system of genes that alter the expression of tumor forming ability, based upon a recent preliminary finding we have made with a pair of Chinese hamster embryo fibroblast cell lines.